9-(4-acetoxy-3-acetoxymethylbutyl)-2-amino-6-fluoropurine | 131266-13-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 9-(4-acetoxy-3-acetoxymethylbutyl)-2-amino-6-fluoropurine
• 英文别名: [2-(Acetyloxymethyl)-4-(2-amino-6-fluoropurin-9-yl)butyl] acetate
• CAS: 131266-13-2
• 化学式: C₁₄H₁₈FN₅O₄
• 分子量: 339.326
• InChiKey: PZYJQTKZGFLHRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  122
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-amino-9-(4-hydroxy-3-hydroxymethylbutyl)-N,N,N-trimethyl-9H-purin-6-aminium chloride 在 4-二甲氨基吡啶 、 potassium fluoride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 9-(4-acetoxy-3-acetoxymethylbutyl)-2-amino-6-fluoropurine
  参考文献：
  名称：

  Synthesis and evaluation of 2-amino-6-fluoro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine mono- and diesters as potential prodrugs of penciclovir

  摘要：

  2-Amino-6-fluoro-9-(4-hydroxy-3-hydroxymethlbut-1-yl)purine (7), and its mono- and diesters 8-15 were prepared and evaluated for their potential as prodrugs of penciclovir. Treatment of 2-amino-6-chloro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine (5) with trimethylamine in THF followed by a reaction of the resulting trimethylammonium chloride salt 6 with KF in DMF afforded 2-amino-6-fluoro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine (7) in 80% yield. Esterification of 7 with an appropriate acid anhydride [Ac2O, (EtCO)(2)O, (n-PrCO)(2)O, or (i-PrCO)(2)O] in DMF in the presence of a catalytic amount of DMAP produced the mono-esters 8-11 in 42-45% yields and diesters 12-15 in 87-99% yields. Of the prodrugs tested in rats, the monoisobutyrate 11 was the most efficiently absorbed and metabolized to 7, showing the mean maximum total concentration of penciclovir (5.5 mu g/mL) and 7 (10.8 mu g/mL) in the blood was much higher than the mean maximum concentration of penciclovir (11.5 mu g/mL) from famciclovir. However, the mean concentrations of penciclovir from it were lower than those from famciclovir because of the limited conversion of a major metabolite 7 to penciclovir by adenosine deaminase. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00263-6

文献信息

• The effect of the c-6 substituent on the regioselectivity of n-alkylation of 2-aminopurines
  作者：Graham R. Geen、Trevor J. Grinter、Peter M. Kincey、Richard L. Jarvest

  DOI：10.1016/s0040-4020(01)87878-9

  日期：1990.1